Process for the preparation of 4-carboxamido-5-cyano-2-imidazolone

ABSTRACT

This invention relates to the synthesis of a unique compound, 4carboxamido-5-cyano-2-imidazolone (may also be called 2-oxo-4cyano-5-imidazolinecarbonamide and by other names) from hydrogen cyanide or from diaminomaleonitrile.

United States Patent Sanchez et al.

[4 1 Feb. 25, 1975 PROCESS FOR THE PREPARATION OF 4-CARBOXAMIDO-5-CYANO-2- IMIDAZOLONE Inventors: Robert A. Sanchez, 867 Riqueza Ave., Encinitas, Calif. 92024; William D. Fuller, 4126 Seri St., San Diego, Calif. 92117 Filed: Mar. 14, 1973 Appl. No.: 341,227

US. Cl 260/309.6, 71/92, 1l7/I39.4,

252/8.8 Int. Cl C07d 49/34 Field of Search 260/3096 References Cited UNITED STATES PATENTS 12/1950 Woodward 260/3096 FOREIGN PATENTS OR APPLICATIONS 936,664 9/l963 Great Britain 260/3095 Primary Examiner-Natalie Trousof Attorney, Agent, or Firm-I. Morley Drucker 6 Claims, N0 Drawings BACKGROUND OF THE INVENTION The resulting product is also unique. It is stable and crystalline and has utility as a plant growth regulator,

as a precursor for many other compounds such as uric acid, and may also be converted to other useful com- D. W. Woodward in US. Pat. NO. 2,534,332 (1950) pounds by conventional techniques.

[Chem. Abstracts, 45, 5791 (1951)] has described the sythesis of 2-oxo-4,5-imidazolinedicarbonitrile and 2- oxo-4,5-imidazolinedicarbonamide, compounds closely related to 4-carboxamido-5-cyano-2- imidazolone (hereinafter referred to by the abbreviation CCl) CCl, by the following reactions:

diaminomaleo phosgene nitrile Both compounds are highly useful. On reacting with formaldehyde and then baking with acid catalysts, colorless water-insoluble resins are produced that are useful as textile crease and shrink-proofing agents.

Reaction with alkali hypohalites by the Hoffmann re- DETAILED DESCRIPTION OF THE INVENTION Diaminomaleonitrile and ammonium bicarbonate react in water to yield CC] directly as a stable crystalline productin good yield (Method A below).

H NC NH zn o 2 1% H NC NH II 2-oxo- 4 5- imidazolinedicarbonitrile Z-oxo- 4 5 imidazolinedicarbonamide CCl is also produced directly when hydrogen cyanide is allowed to undergo base-catalyzed polymerization in the presence of ammonium bicarbonate (Method B below.) These reactions are illustrated in the following scheme:

II H N CC H NC H N NH nco N C C=N NEC H diaminomaleonitrile 4-carboxamido-5-cyano-2- imidazo lone "CCI" CN NH HCO I SUMMARY OF THE INVENTION This invention relates to a method of production of CCl in good to excellent yield by reacting a watersoluble bicarbonate salt with either hydrogen cyanide or HCN tetramer. in aqueous alkaline media, preferably of a pH of 7-9 and at ambient temperatures. The reaction is unique and unexpected.

Since the polymerization of cyanide in a basic catalyst system is known to produce diaminomaleonitrile (see co-pending patent application of Robert A. Sanchez, Ser. No. 313,137 filed on Dec. 13, 1972 and incorporated herein by this reference) CCl may be readily formed from diaminomaleonitrile by utilizing this latter method.

These methods are extremely simple and economical for the synthesis of CCl, for no solvent is needed other than water, and ammonium bicarbonate is very inexpensive and easy to handle.

Water soluble salts other than ammonium bicarbonate may be used in the synthesis (e.g. sodium bicarbonate, potassium bicarbonate, etc.) and are understood to be included in the scope of this invention. When utilizing neutral salts, the aqueous media should be made slightly basic, i.e., between about 7-9. Ammonium bicarbonate is usually preferable by virtue of its high solubility, and the fact that its basicity is about 8.

The pH of the reaction medium in both methods is preferably maintained in the range of about 7-9, and no additional catalyst is required. At lower pHs there is a tendency for carbon dioxide gas to be released, and at higher pHs diaminomaleonitrile becomes less stable.

It is preferred that the bicarbonate be present in about a 4:1 molar ratio with respect to the diaminomaleonitrile, although the molar ratios can range between 1:1 or greater.

The reactions may be carried out most conveniently at ambient temperature (-40 C) although temperatures in the proximate range of 0l0OC are permissible. At the higher temperatures pressure vessels may be necessary to control the loss of carbon dioxide or HCN.

The product (CCl) may be readily converted to ei ther the dicarbonitrile or dicarbonamide derivatives of Woodward (loc. cit.) by any ofa number of well known methods (e.g. dehydration with phosphorous oxychloride and alkaline hydrolysis, respectively). More importantly, CCl itself may be used directly in many of the conversions for which the dicarbonitrile and dicarbonamide have established utility. We have further shown that CCI itself is a plant growth regulator in that the germination time of peas may be reduced by more than in its presence.

EXAMPLES OF THE INVENTION Example 1 A suspension of 54g (0.50 moles) of diaminomalconitrile in 2 liters of 2M NH HCO was stirred at room temperature (ca 22C) for l day. The insoluble tan product was filtered off, washed with a little cold water, with ethanol and then with ether. After drying under'high vacuum over P 05 the CC1 weighed 65g (97% yield). The product was homogeneous as shown be descending paper chromatography in butanol-water (R 0.40) and in butanol-acetic acid-water (R, 0.58). A white product of high purity was obtained by dissolving in aqueous KOH, filtering through activated charcoal and then acidifying with HCl. On heating, the compound darkens at around 300C but does not melt below 400C.

Elemental microanalysis gave the following results: Calculated for CCI (C,-,H N.,O MW 152.1): C,39.47%; H,2.63%; N,36.83%

Found: C,39.04%; H,2.67%; N,36.79%

The ultraviolet spectrum in water showed the follow ing absorption maxima:

pH 1-6, 286 nm; pH 10, 310 nm; pH 13, 331 nm This type of spectrum is typical of structures such as CCI. The dicarbonitrile of Woodward (loc. cit) for example shows:

pH 1-6, 284 nm; pH 10, 303 nm; pH 13, 318 nm The infrared spectrum (KBr wafer) is fully consistent with the CC1 structure. showing for example a single C N frequency at 2.240 cm and -C=O frequencics at l,670-l.710 cm"" The nuclear magnetic resonance spectrum (DMSO d) is also consistent, showing only NH resonances (no -H detectable).

Final proof of structure is provided by direct comparison with Woodward's compounds (loc. cit). Alkaline hydrolysis of Woodward's dicarbonitrile yields CCl directly as a major initial product, as revealed by descending paper chromatography in three different solvent systems and by the ultraviolet spectrum of the I product. Extended alkaline hydrolysis of Woodwards dicarbonitrile and of CCI result in the formation of identical later products, presumably the dicarbonamide and finally the dicarboxylic acid.

A detailed analysis of our CCI synthesis reveals that Woodards dicarbonitrile is not an intermediate, as might be presumed. Thus, at no time during the reaction of diaminomaleonitrile with ammonium bicarbonate is any trace of the dicarbonitrile detectable by either thin layer chromatography or paper chromatography. Furthermore, we have shown that the dicarbonitrile is not converted to CC] under the conditions of our synthesis. Consequently, our synthesis is wholly independent of Woodwards compounds.

Example 2 The following experiment illustrates the plant growth regulating properties of CCI.

Pea seeds in a humus mix were irrigated daily with 2-3 ml. of water alone (control), water containing diaminomaleonitrile (lO' M, l0 M, lO M) and water containing CCl (10 M, lO' M, 10 M).

With the water controls and with the diaminomaleonitrile solutions (10 seeds per experiment) average germination times as measured by surfacing of the seedlings were identical within experimental error (i2%). With CCI germination times were reduced by 23% at lO M, 17% at l0 M and 4% at 10 M.

Example 3 Several experiments were conducted in which aqueous solutions of ammonium cyanide (l-lOM) were allowed to polymerize at room temperature with and without the presence of ammonium bicarbonate. Without ammonium bicarbonate the synthesis of diaminomaleonitrile could be detected both by chromatographic techniques and by ultraviolet spectroscopy. ln the presence of ammonium bicarbonate little or no diaminomaleonitrile could be detected, but in its place CCI was being formed'in approximately equal yields to the amount of tetramer that would be formed in the absence of ammonium bicarbonate.

The CCl was identified by its thin layer and paper chromatographic R, values and by its ultraviolet spectrum.

Modifications of the foregoing which fall within the scope of the invention will become apparent to those skilled in the art. We intend, therefore, to be bound only by the claims which follow.

We claim:

1. A process for the production of 4-carboxamido-5- cyano-2-imidazolone which comprises the steps of:

reacting a water-soluble bicarbonate salt with a member of the group selected from hydrogen cyanide and diaminomaleonitrile, in aqueous alkaline media having a pH of between about 7 to about 9 and a temperature of between about 10-40C to form 4-carboxamido-5-cyano-2-imidazolone.

2. The process of claim 1 wherein the water-soluble bicarbonate salt is ammonium bicarbonate.

3. The process of claim 1 wherein said water-soluble bicarbonate salt is potassium bicarbonate.

4. The process of claim 1 wherein said water-soluble bicarbonate salt is sodium bicarbonate.

5. The process of claim 1 wherein the molar propor tion of said bicarbonate salt to said diaminomaleonitrile lies in excess of 1:1 or greater.

6. The process of claim 1 wherein said reaction is conducted at ambient temperature. 

1. A PROCESS FOR THE PRODUCTION OF 4-CARBOXAMIDO-5-CYANO2-IMIDAZOLONE WHICH COMPRISES THE STEPS OF: REACTING A WATER-SOLUBLE BICARBONATE SALT WITH A MEMBER OF THE GROUP SELECTED FROM HYDROGEN SALT WITH A MEMBER OF DIAMINOMALEONITRILE, IN AQUEOUS HYDROGEN MEDIA HAVING A PH OF BETWEEN ABOUT 7 TO ABOUT 9 AND A TEMPERATURE OF BETWEEN ABOUT 10*-40*C TO FROM 4-CARBOXAMIDO-5CYANO-2-IMIDAZOLONE.
 2. The process of claim 1 wherein the water-soluble bicarbonate salt is ammonium bicarbonate.
 3. The process of claim 1 wherein said water-soluble bicarbonate salt is potassium bicarbonate.
 4. The process of claim 1 wherein said water-soluble bicarbonate salt is sodium bicarbonate.
 5. The process of claim 1 wherein the molar proportion of said bicarbonate salt to said diaminomaleonitrile lies in excess of 1: 1 or greater.
 6. The process of claim 1 wherein said reaction is conducted at ambient temperature. 